Pharmacokinetic/pharmacodynamic assessment of a novel,pharmaceutical lipid–aspirin complex: results of a randomized,crossover, bioequivalence study

Journal of Thrombosis and Thrombolysis - Aspirin (acetylsalicylic acid, ASA) can lead to gastrointestinal mucosal injury through disruption of its protective phospholipid bilayer. A liquid...     

Clinical trial: comparison of ibuprofen-phosphatidylcholine and ibuprofen on the gastrointestinal safety and analgesic efficacy in osteoarthritic patients

Background  Chronic use of NSAIDs is associated with gastrointestinal (GI) toxicity that increases with age.
Aim  To evaluate the GI safety and therapeutic efficacy of ibuprofen chemically associated with phosphatidylcholine (PC) in osteoarthritic (OA) patients.
Methods  A randomized, double-blind trial of 125 patients was performed. A dose of 2400 mg/day of ibuprofen or an equivalent dose of ibuprofen-PC was administered for 6 weeks. GI safety was assessed by endoscopy. Efficacy was assessed by scores of analgesia and anti-inflammatory activity. Bioavailability of ibuprofen was pharmacokinetically assessed.
Results  Ibuprofen-PC and ibuprofen provided similar bioavailability/therapeutic efficacy. In the evaluable subjects, a trend for improved GI safety in the ibuprofen-PC group compared with ibuprofen that did not reach statistical significance was observed. However, in patients aged >55 years, a statistically significant advantage for ibuprofen-PC treatment vs. ibuprofen in the prevention of NSAID-induced gut injury was observed with increases in both mean Lanza scores and the risk of developing >2 erosions or an ulcer. Ibuprofen-PC was well tolerated with no major adverse events observed.
Conclusion  Ibuprofen-PC is an effective osteoarthritic agent with an improved GI safety profile compared with ibuprofen in older OA patients, who are most susceptible to NSAID-induced gastroduodenal injury.     

Bioavailability of aspirin in fasted and fed states of a novel pharmaceutical lipid aspirin complex formulation

Journal of Thrombosis and Thrombolysis - Dyspeptic symptoms are common with aspirin and clinicians frequently recommend that it be taken with food to reduce these side effects. However, food can...     

The Fanconi anemia complementation group C protein corrects DNA interstrand cross-link-specific apoptosis in HSC536N cells

Fanconi anemia (FA) cells are hypersensitive to cytotoxicity, cell cycle arrest, and chromosomal aberrations induced by DNA cross-linking agents, such as mitomycin C (MMC) and nitrogen mustard (HN2). Although MMC hypersensitivity is complemented in a subset of FA cells (complementation group C [FA-C]) by wild-type FAC cDNA, the cytoprotective mechanism is unknown. In the current study, we tested the hypothesis that FAC protein functions in the suppression of DNA interstand cross-link (ISC)-induced cell cycle arrest and apoptosis. Comparison of HN2-induced cell cycle arrest and apoptosis with those of its non-cross-linking analogs, diethylaminoethyl chloride and 2- dimethylaminoethyl chloride, delineated the DNA ISC specificity of FAC- mediated cytoprotection. Overexpression of wild-type FAC cDNA in FA-C lymphoblasts (HSC536N cell line) prevented HN2-induced growth inhibition, G2 arrest, and DNA fragmentation that is characteristic of apoptosis. In contrast cytoprotection was not conferred against the effects of the non-cross-linking mustards. Our data show that DNA ISCs induce apoptosis more potently than do DNA monoadducts and suggest that FAC suppresses specifically DNA ISC-induced apoptosis in the G2 phase of the cell cycle.